Crystallographic structure of an intact IgG1 monoclonal antibody.
The structure of an intact monoclonal antibody for phenobarbital, subclass IgG1, has been determined to 3.2 A resolution by X-ray crystallography. The molecule was visualized in a monoclinic unit cell having an entire immunoglobulin as the asymmetric unit. The two Fab segments, both with elbow angles of 155 degrees , were related by a rotation of 179.7 degrees plus a translation along the approximate dyad of 9 A. This is the first observation of such an Fab translation in a structurally defined antibody. The approximate 2-fold of the Fc was independent of that relating Fabs, making an angle of 107 degrees with the Fab dyad. The angle between long axes of the Fabs was 115 degrees, the most acute angle yet observed, yielding a distorted Y shaped molecule. This is in contrast to the distorted T shape of the only other intact IgG (2a) whose complete structure is known. Primary lattice interactions arise through formation of VH antiparallel beta ribbons whose strands are contributed by pseudo dyad related H2, and by L3 hypervariable loops from neighboring molecules. While one CH2 domain was mobile, Fabs and three domains of the Fc were well defined, as were hinge polypeptides connecting Fabs to the Fc, and the covalently attached oligosaccharides. Direct interactions are observed between hinge polypeptides, the glycosylated loop of one CH2 domain, and the oligosaccharide. Lattice interactions clearly influence, perhaps even determine the overall conformation of the antibody observed in this crystal. Comparison of this IgG1 with previously determined intact antibody structures extends the conformational range arising from segmental flexibility.
Harris
L J
LJ
Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.
Skaletsky
E
E
McPherson
A
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000927:Anticonvulsants / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry; D003461:Crystallography; D007074:Immunoglobulin G / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000276:immunology; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000927:Anticonvulsants; D002241:Carbohydrates; D007074:Immunoglobulin G; D010634:Phenobarbital